Preterm (or premature) labor is the second most important reason for fetal morbidity and mortality after fetal anomalies, occurring in about 10 percent of all pregnancies (8-12% of all labors in the US are premature. The total annual number of premature deliveries is about 400,000). Preterm labor is usually defined as the onset of labor before 37 weeks of pregnancy have been completed. The symptoms of preterm labor include uterine contractions at regular intervals that begin before the fetus is mature, usually before the due date of delivery, passage of bloody mucus, flow of fluid (amniotic fluid) from the uterus, that may occur with a gush or may be only a continuous watery discharge.
Main causes of preterm labor include premature rupture of the amniotic membranes (xe2x80x9cwater breaksxe2x80x9d), illness of the mother, including pre-eclampsia, high blood pressure or diabetes, abnormal shape or size of the uterus, weak or short cervix, hormone imbalance, vaginal infection that spreads to the uterus, large fetus or more than one fetus, abnormalities of the placenta, such as placenta previa, and excessive amniotic fluid.
Tocolytic agents (medications used to inhibit labor), such as Beta-adrenergic agents, Magnesium sulfate, Prostaglandin inhibitors, Calcium channel blocker, are usually used to treat preterm labor and permit pregnancy to proceed so that the fetus can gain more size and maturity before delivery.
However, it was found that tocolytic agents are effective only in short term (up to 72 h) with efficacy of 40-50%. Moreover, they present severe adverse effects for both mother and fetus.
Cervical cerclage, on the other hand, have long term efficacy, but is a relevant therapy for only 2-4% of all preterm labor cases, and comprises surgical intervention.
Itis not always possible to inhibit labor contractions and stop the labor process by drugs. Moreover, the efficiency of drugs on the inhibition of labor is low, and is associated with many adverse effects (even cervical cerclage in small percentage of patients).
Electric muscle control is not a new concept, dating back to Galvani""s experiments, applying electrical field to a dead frog""s leg and causing its twitching (Galvani himself thought it to be the result of the generation of electricity in the dead animal""s leg). For example, PCT/IL97/00012 (Ben-Haim et al.), published as WO 97/25098 and titled ELECTRICAL MUSCLE CONTROLLER now U.S. Pat. No. 6,363,279) described an electrical muscle controller for applying non-excitatory electric stimulation of the cardiac muscle in order to gain enhanced contractility, all incorporated herein by reference. It is noted that by xe2x80x9cnon-excitatory electric stimulationxe2x80x9d it is meant electric stimulation that does not initiate electrical activation signal. An activation signal is an electrical signal which, when it reaches an excitable cell, causes it to depolarize and perform its destined activity.
In PCT/IL97/00243 published as WO 99/03533, titled SMOOTH MUSCLE CONTROLLER, there was described a method of directly and locally controlling the contraction and the force of contraction of smooth muscles.
The uterus muscle is also a smooth muscle that contracts in response to electrical activation signals. The uterus wall is composed of myometrium tissue, which is excitable and suitable for excitable tissue control (ETC) therapy of motion modulation through electrical non-stimulatory signal. See: xe2x80x9cUterine Electromyography: A Critical Reviewxe2x80x9d, by D. Deveduex et al., Am. J. Obstet Gynecol 1993, 169, 1636-53.
U.S. Pat. No. 5,447,526 (Karsdon), filed in 1992, titled TRANSCUTANEOUS ELECTRIC MUSCLE/NERVE CONTROLLER/FEEDBACK UNIT, described a transcutaneous device for inhibiting uterine contractions. It comprises a first plurality electrode positioned on an anterior side of an abdomen of a patient, extending laterally above an upper portion of the uterus, a second plurality electrode positioned on the anterior side of the abdomen of the patient, extending laterally on the mid to lower portion of the uterus. U.S. Pat. No. 5,964,789 (Karsdon) and U.S. Pat. No. 5,713,940 (Karsdon) describe similar versions of devices as in U.S. Pat. No. 5,447,526.
Karsdon explains that as opposed to prior art electrical control devices, which are generally aimed at stimulating or increasing muscle activity, his devices are aimed at inhibiting muscular activity. Karsdon explains that his devices employ relatively long electrical pulses with a plurality of wave patterns, and constant current output.
U.S. Pat. No. 5,991,649 (Garfield et al.), filed in 1996, titled METHODS FOR ACTIVATING THE MUSCLE CELLS OR NERVES OF THE UTERUS OR CERVIX, also described electrical control of uterus activity.
It is established that both Karsdon and Garfield suggest applying excitatory signals to the uterus (given the suggested length of the applied signals, as well as explicit mentioningxe2x80x94by Garfieldxe2x80x94of the action potential propagation).
But although the concept of inhibiting labor contractions, using electrical signals, per se, is not entirely new, the present invention suggests an entirely novel approach to induction of labor using non-excitatory electrical stimulation.
Prior art methods of inducing labor included natural methods, such as rupturing the membranes, stripping the membranes during pelvic examination, nipple stimulation to release one""s own natural oxytocin, administration of enema or drinking castor oil, and even just walking. Application of drugs that cause induced labor in the event of failure to commence spontaneous labor is carried out if these natural methods fail.
Commonly labor inducing drugs include oxytocin, pitocin (a synthetic form of oxytocin) given intravenously or Prostaglandin (usually in the form of gel or suppository).
Oxytocin causes prelabor contractions to increase both in amplitude and in rhythm. But although increased contraction amplitude is desirable, increased contraction rhythm may result in fetus stress. During strong contractions the fetus is pressed inside the uterus, its navel cord may be squeezed, and as a result the oxygen supply may be temporarily halted or severely reduced. In naturally rhythmic labor contractions the fetus is given enough time to recover, but if the pace of the contractions is speeded up serious irreversible damage may occur. Fetus stress can be monitored using commonly available monitoring devices (where usually the fetus heart rate as well as other parameters are tracked).
The correct dose of oxytocin is not initially known and varies from patient to patient. It depends, inter alia, on the readiness of the uterus for labor, and therefore administering over dose of oxytocin is not uncommon. Over dose of oxytocin may result in extreme cases in tearing of the uterus due to violent hypertonic contractions. As the duration of the oxytocin effect is determined by the given dose and the half life period (typically 3-5 minutes), the only way to cancel oxytocin effect before the wash-out period is by administering a tocolytic drug.
The present invention seeks to provide novel method and device for inhibiting or enhancing and even initiating uterus contractions, i.e. inhibiting preterm labor or inducing or expediting labor in overdue pregnancy.
In our PCT/IL97/00243 published as WO 99/03533 there was disclosed (see also FIGS. 6-8 in that patent application) a device for inhibiting premature labor or stimulating labor contractions. It was stipulated that such device may provide more control over the process of labor than is possible by using drugs.
Several situations were considered:
a. stopping premature labor;
b. stopping a labor where a cesarean section is indicated;
c. situations where fine control of the force of contractions of the uterus is required;
d assisting a labor which is not advancing properly;
e. stopping labor from ever starting, where it is contra-indicated;
f dictating a preferred contraction profile during labor.
It is a main object of the present invention to provide uterus controlling device and method that provides for induction of labor, even where it has not begun.
Another main purpose of the present invention is to provide uterus controlling device and method for inhibition of labor contractions.
Another object of the invention is to provide such device and method that allows for refined control of the uterus, governing the amplitude, timing, duration of the uterus contractions, thus achieving substantial control over labor, either initiating, enhancing or inhibiting labor contractions.
Yet another object of the invention is to provide several modes of operation of such device and method so as to accomplish various goals and objects relating to labor and control of the uterus.
There is thus provided, in accordance with a preferred embodiment of the present invention, a method for controlling uterine contractions in a female comprising:
providing at least one of a plurality of sensors adapted to sense uterine contractions;
providing an electric signal generator;
providing a control unit adapted to receive the signal from said at least one of a plurality of sensors and actuate said signal generator to generate a non-excitatory electric signal in a predetermined timing and duration with respect to a sensed uterine contraction;
providing electric signal delivery means for the delivery of electric signal from the electric signal generator to at least one of a plurality of predetermined locations on the uterus;
sensing a uterine contraction using said at least one of a plurality of sensors; and
applying non-excitatory electric field at said at least one of a plurality of predetermined locations on the uterus in predetermined timing and duration with respect to the sensed uterine contraction.
Furthermore, in accordance with another preferred embodiment of the present invention, there is provided a method for enhancing uterine contractions in a female comprising:
providing at least one of a plurality of sensors adapted to sense uterine contractions;
providing an electric signal generator;
providing a control unit adapted to receive the signal from said at least one of a plurality of sensors and actuate said signal generator to generate a non-excitatory electric signal in a predetermined timing and duration with respect to the sensed uterine contraction;
providing electric signal delivery means for the delivery of electric signal from the electric signal generator to at least one of a plurality of predetermined locations on the uterus;
sensing a uterine contraction using said at least one of a plurality of sensors; and
applying non-excitatory electric field at said at least one of a plurality of predetermined locations on the uterus in a predetermined timing and duration with respect to the sensed uterine contraction.
Furthermore, in accordance with another preferred embodiment of the present invention, there is provided a method for controlling uterine contractions in a female comprising:
providing at least one of a plurality of sensors adapted to sense uterine contractions;
providing an electric signal generator;
providing a control unit adapted to receive the signal from said at least one of a plurality of sensors and actuate said signal generator to generate a non-excitatory electric signal in a predetermined timing and duration with respect to the sensed uterine contraction;
providing electric signal delivery means for the delivery of electric signal from the electric signal generator to at least one of a plurality of predetermined locations on the uterus;
sensing a uterine contraction using said at least one of a plurality of sensors; and
applying non-excitatory electric field at said at least one of a plurality of predetermined locations on the uterus in a predetermined timing and duration with respect to the sensed uterine contraction, said electric field commencing not before the commencement of the uterine contraction.
Furthermore, in accordance with another preferred embodiment of the present invention, the method is used for enhancing uterine contractions, and the non-excitatory electric field is terminated not later than the end of a peaked substantially plateau level in said contraction.
Furthermore, in accordance with another preferred embodiment of the present invention, said at least one of a plurality of sensors is a sensing electrode and wherein the commencement of the contraction is determined by the commencement of erratic electric activity of the uterus sensed by the sensing electrode and the estimated end of a plateau level in said contraction may be determined automatically or manually by the physician by determining the termination of the erratic electric activity.
Furthermore, in accordance with another preferred embodiment of the present invention, said at least one of a plurality of sensors is an intra-uterine pressure sensor and wherein the commencement of the contraction is determined by the commencement of rise in the pressure activity of the uterus sensed by the intrauterine pressure sensor and the end of a plateau level in said contraction is determined by a drop in the intra-uterine pressure level following the peaked substantially plateau level.
Furthermore, in accordance with another preferred embodiment of the present invention, the duration of the applied non-excitatory electric field is not greater than about 10 percent of the duration of the contraction cycle.
Furthermore, in accordance with another preferred embodiment of the present invention, the non-excitatory electric field is applied with a delay after the commencement of the uterine contraction.
Furthermore, in accordance with another preferred embodiment of the present invention, the non-excitatory electric field comprises a substantially constant non-excitatory electric field.
Furthermore, in accordance with another preferred embodiment of the present invention, the substantially constant non-excitatory electric field is stopped before the anticipated commencement of a uterine contraction.
Furthermore, in accordance with another preferred embodiment of the present invention, said electric field has a square waveform.
Furthermore, in accordance with another preferred embodiment of the present invention, said electric field has a trapezoidal waveform.
Furthermore, in accordance with another preferred embodiment of the present invention, said electric field ends in a gradual drop.
Furthermore, in accordance with another preferred embodiment of the present invention, the gradual drop is linear.
Furthermore, in accordance with another preferred embodiment of the present invention, the gradual drop is non-linear.
Furthermore, in accordance with another preferred embodiment of the present invention, said plurality of sensors comprise sensing electrodes for measuring electromyography (EMG) signals.
Furthermore, in accordance with another preferred embodiment of the present invention, in order to synchronize output waves to uterine contractions at least one of said plurality of sensors is placed on the abdomen of the female.
Furthermore, in accordance with another preferred embodiment of the present invention, said plurality of sensors comprise intra-uterine pressure sensors.
Furthermore, in accordance with another preferred embodiment of the present invention, said plurality of sensors comprise mechanical sensors.
Furthermore, in accordance with another preferred embodiment of the present invention, said mechanical sensors comprise strain gauge sensors.
Furthermore, in accordance with another preferred embodiment of the present invention, said strain gauge sensors are placed on the abdomen of the female.
Furthermore, in accordance with another preferred embodiment of the present invention, said at least one of a plurality of sensors is inserted vaginally and placed in contact with the cervix.
Furthermore, in accordance with another preferred embodiment of the present invention, said electric signal delivery means comprise at least one of a plurality of electrodes.
Furthermore, in accordance with another preferred embodiment of the present invention, said electrodes are selected from stitch electrodes, patch electrodes, net-like electrodes.
Furthermore, in accordance with another preferred embodiment of the present invention, said electrodes are deployed transcutanouesly.
Furthermore, in accordance with another preferred embodiment of the present invention, said electrodes are deployed vaginally.
Furthermore, in accordance with another preferred embodiment of the present invention, said at least one of a plurality of electrodes is placed in the fundus vicinity.
Furthermore, in accordance with another preferred embodiment of the present invention, said control unit continuously samples said at least one of a plurality of sensors input and estimates the timing of initiation of said sensed contractions, the magnitude of said sensed contractions, and the rhythm of said contractions, whereby the magnitude of the contractions, and the rhythm of sensed contractions are used to estimate the progression of the labor process in time to determine a necessity for any electrical intervention or determine the need to terminate the therapy.
Furthermore, in accordance with another preferred embodiment of the present invention, said non-excitatory electric field is applied in synchrony with the sensed uterine contractions.
Furthermore, in accordance with another preferred embodiment of the present invention, said control unit is programmable.
Furthermore, in accordance with another preferred embodiment of the present invention, the non-excitatory electric field is applied in duration in the range of 100 milliseconds to 5 seconds.
Furthermore, in accordance with another preferred embodiment of the present invention, the non-excitatory electric field strength is in the range of 500 microamperes to 20 milliamperes.
Furthermore, in accordance with another preferred embodiment of the present invention, the non-excitatory electric field strength is in the range of 2 to 6 milliamperes.
Furthermore, in accordance with another preferred embodiment of the present invention, the method is used for slowing the rhythm of contractions but substantially retaining the amplitude of contractions, wherein the non-excitatory electric field duration is in the range of 6 to 10 seconds.
Furthermore, in accordance with another preferred embodiment of the present invention, the method is used for inhibiting uterine contractions, wherein the non-excitatory electric field is in the range of 10 seconds to 100 seconds.
Furthermore, in accordance with another preferred embodiment of the present invention, the method is applied in conjunction with drug therapy.
Furthermore, in accordance with another preferred embodiment of the present invention, there is provided a device for controlling uterine contractions comprising:
at least one of a plurality of sensors adapted to sense uterine contractions;
an electric signal generator; and
a control unit adapted to receive signals from said sensors and actuate said signal generator in a predetermined manner.
Furthermore, in accordance with another preferred embodiment of the present invention, said electric signal generator is adapted to generate a substantially constant non-excitatory electric field.
Furthermore, in accordance with another preferred embodiment of the present invention, said electric signal generator is adapted to occasionally switch the polarity of said non-excitatory electric field so as to reduce ionic polarization effects.
Furthermore, in accordance with another preferred embodiment of the present invention, said electric signal generator is adapted to stop said substantially constant non-excitatory electric field before the anticipated commencement of a uterine contraction.
Furthermore, in accordance with another preferred embodiment of the present invention, said electric signal generator is adapted to apply the non-excitatory electric field in synchrony with the sensed uterine contractions.
Furthermore, in accordance with another preferred embodiment of the present invention, the electric signal generator is adapted to apply said non-excitatory electric field with a time delay with respect to the commencement of a uterine contraction.
Furthermore, in accordance with another preferred embodiment of the present invention, said plurality of sensors comprise sensing electrodes for measuring EMG signals.
Furthermore, in accordance with another preferred embodiment of the present invention, at least one of said plurality of sensors is adapted to be placed on the abdomen of the female in order to synchronize output waves to spontaneous uterine contractions.
Furthermore, in accordance with another preferred embodiment of the present invention, said plurality of sensors comprise intrauterine pressure sensors.
Furthermore, in accordance with another preferred embodiment of the present invention, said plurality of sensors comprise mechanical sensors.
Furthermore, in accordance with another preferred embodiment of the present invention, said mechanical sensors comprise strain gauge sensors.
Furthermore, in accordance with another preferred embodiment of the present invention, said strain gauge sensors are adapted to be placed on the abdomen of the female.
Furthermore, in accordance with another preferred embodiment of the present invention, said at least one of a plurality of sensors is adapted to be inserted vaginally and placed in contact with the cervix.
Furthermore, in accordance with another preferred embodiment of the present invention, said electric signal delivery means comprise at least one of a plurality of electrodes.
Furthermore, in accordance with another preferred embodiment of the present invention, said electrodes are selected from stitch electrodes, patch electrodes, net-like electrodes.
Furthermore, in accordance with another preferred embodiment of the present invention, said electrodes are adapted to be deployed transcutanouesly.
Furthermore, in accordance with another preferred embodiment of the present invention, said electrodes are adapted to be deployed vaginally.
Furthermore, in accordance with another preferred embodiment of the present invention, said at least one of a plurality of electrodes is adapted to be placed in the fundus vicinity.
Furthermore, in accordance with another preferred embodiment of the present invention, said control unit is adapted to continuously sample said at least one of a plurality of sensors input and estimate the timing of initiation of said sensed contractions, the magnitude of said sensed contractions, and the rhythm of said contractions, whereby the magnitude of the contractions, and the rhythm of contractions are used to estimate the progression of the labor process in time to determine a necessity for any electrical intervention or determine the need to stop the therapy.
Furthermore, in accordance with another preferred embodiment of the present invention, said control unit is programmable.
Furthermore, in accordance with another preferred embodiment of the present invention, said electric signal generator is adapted to generate electric field having a square waveform.
Furthermore, in accordance with another preferred embodiment of the present invention, said electric signal generator is adapted to generate electric field having a trapezoidal waveform.
Furthermore, in accordance with another preferred embodiment of the present invention, said electric signal generator is adapted to generate electric field that ends in a gradual drop.
Furthermore, in accordance with another preferred embodiment of the present invention, the electric signal generator is adapted to generate a non-excitatory electric field having a duration in the range of 100 milliseconds to 5 seconds.
Furthermore, in accordance with another preferred embodiment of the present invention, the electric signal generator is adapted to generate a non-excitatory electric field of a strength in the range of 500 microamperes to 20 milliamperes.
Furthermore, in accordance with another preferred embodiment of the present invention, the electric signal generator is adapted to generate a non-excitatory electric field of a strength in the of 2 to 6 milliamperes.
Furthermore, in accordance with another preferred embodiment of the present invention, the device is designed for slowing the rhythm of contractions but substantially retaining the amplitude of contractions, wherein the electric signal generator is adapted to generate a non-excitatory electric field with duration in the range of 6 to 10 seconds.
Finally, in accordance with another preferred embodiment of the present invention, the device is designed for inhibiting uterine contractions, wherein the electric signal generator is adapted to generate a non-excitatory electric field in the range of 10 seconds to 100 seconds.